1. Field of the Invention
This invention relates to compounds which are useful as interferon potentiators and polyamine biosynthesis inhibitors.
2. Background of the Invention
Interferon is a protein which exhibits antitumor and antiviral as well as a wide range of other biological activities. The advent of recombinant DNA technology has permitted the production of large quantities of interferon for a variety of therapeutic applications, including antitumor and antiviral treatments. The synthesis of polyamines, such as putrescine, spermidine and spermine, is important in cellular replication. In biological systems, these polyamines are synthesized by spermidine synthase and spermine synthase. Potentiators of interferon antitumor and antiviral activity and inhibitors spermidine synthase are of interest to the medical field.
U.S. Pat. No. 4,376,116 discloses a compound having the formula ##STR1## wherein
R is PA2 CH--(CH.sub.2).sub.5 NHR' PA2 (CH.sub.2).sub.2 --NH.sub.2
wherein R' is hydrogen or aminopropyl and salts thereof. The compounds are said to be specific inhibitors for enzyme catalyzed alkyl transfer reactions involving the enzymes spermidine synthase and spermine synthase. The reference also discloses methods for treating cystic fibrosis and subjects having a parasitic infection.
Sunkara et al., Science, 219:851 (1983) discloses tumor suppression with a combination of .alpha.-difluoromethyl ornithine (DFMO) with interferon. The reference discloses that DFMO is an irreversible inhibitor of othnithine decarboxylase, the first step in polyamine synthesis. The reference further discloses that DFMO in combination with interferon gave total or near total suppression of tumor growth of B16 melanoma cells.